tbuckley/cabot-search huggingface dataset:
Adjuvant Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non–muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial
Authors: Wei Shen Tan, Aaron Prendergast, Charlotte Ackerman, Yathushan Yogeswaran, Joanne Cresswell, Paramananthan Mariappan, Jaspal Phull, Paul Hunter-Campbell, Henry Lazarowicz, Vibhash Mishra, Abhay Rane, Melissa Davies, Hazel Warburton, Peter Cooke, Hugh Mostafid, Daniel Wilby, Robert Mills, Rami Issa, John D. Kelly
Journal: European Urology (2022)

Adjuvant intravesical chemotherapy following tumour resection is recommended for intermediate-risk non-muscle-invasive bladder cancer (NMIBC).To assess the efficacy and safety of adjuvant intravesical chemohyperthermia (CHT) for intermediate-risk NMIBC.HIVEC-II is an open-label, phase 2 randomised controlled trial of CHT versus chemotherapy alone in patients with intermediate-risk NMIBC recruited at 15 centres between May 2014 and December 2017 (ISRCTN 23639415). Randomisation was stratified by treating hospital.Patients were randomly assigned (1:1) to adjuvant CHT with mitomycin C at 43°C or to room-temperature mitomycin C (control). Both treatment arms received six weekly instillations of 40 mg of mitomycin C lasting for 60 min.The primary endpoint was 24-mo disease-free survival as determined via cystoscopy and urinary cytology. Analysis was by intention to treat.A total of 259 patients (131 CHT vs 128 control) were randomised. At 24 mo, 42 patients (32%) in the CHT group and 49 (38%) in the control group had experienced recurrence. Disease-free survival at 24 mo was 61% (95% confidence interval [CI] 51-69%) in the CHT arm and 60% (95% CI 50-68%) in the control arm (hazard ratio [HR] 0.92, 95% CI 0.62-1.37; log-rank p = 0.8). Progression-free survival was higher in the control arm (HR 3.44, 95% CI 1.09-10.82; log-rank p = 0.02) on intention-to-treat analysis but was not significantly higher on per-protocol analysis (HR 2.87, 95% CI 0.83-9.98; log-rank p = 0.06). Overall survival was similar (HR 2.55, 95% CI 0.77-8.40; log-rank p = 0.09). Patients undergoing CHT were less likely to complete their treatment (n =75, 59% vs n = 111, 89%). Adverse events were reported by 164 patients (87 CHT vs 77 control). Major (grade III) adverse events were rare (13 CHT vs 7 control).CHT cannot be recommended over chemotherapy alone for intermediate-risk NMIBC. Adverse events following CHT were of low grade and short-lived, although patients were less likely to complete their treatment.The HIVEC-II trial investigated the role of heated chemotherapy instillations in the bladder for treatment of intermediate-risk non-muscle-invasive bladder cancer. We found no cancer control benefit from heated chemotherapy instillations over room-temperature chemotherapy. Adverse events following heated chemotherapy were low grade and short-lived, although these patients were less likely to complete their treatment.
Prevention of Bacterial Endocarditis
Authors: Adnan S. Dajani
Journal: JAMA (1990)

SURGICAL and dental procedures and instrumentations involving mucosal surfaces or contaminated tissue commonly cause transient bacteremia that rarely persists for more than 15 minutes. Blood-borne bacteria may lodge on damaged or abnormal heart valves or on the endocardium or the endothelium near congenital anatomic defects, resulting in bacterial endocarditis or endarteritis. Although bacteremia is common following many invasive procedures, only a limited number of bacterial species commonly cause endocarditis. It is impossible to predict which patient will develop this infection or which particular procedure will be responsible. Certain cardiac conditions are more often associated with endocarditis than others (Table 1). Furthermore, certain dental and surgical procedures are much more likely to initiate the bacteremia that results in endocarditis than are other procedures (Table 2). Prophylactic antibiotics are recommended for patients at risk for developing endocarditis who are undergoing those procedures most likely to produce bacteremia with organisms that commonly cause
Significant factors influencing chronic postoperative inguinal pain: A conditional time-dependent observational cohort study
Authors: L.M. van den Dop, F.P.J. den Hartog, D. Sneiders, G. Kleinrensink, J.F. Lange, J.F. Gillion
Journal: International Journal of Surgery (2022)

Inguinal hernia (IH) repair is a common surgical procedure. Focus has shifted from recurrences to chronic postoperative inguinal pain (CPIP). To assess the natural course of CPIP and identify patient factors influencing the onset of CPIP, an observational registry-based study was performed.Data prospectively collected from the Club-Hernie national database was retrieved from 2011 until 2021. Patients who underwent elective surgery for inguinal hernia were divided in an irrelevant pain group and relevant pain group. Relevant pain at one year and two years were compared with patients with irrelevant pain at all-time points (preoperatively, one month, one year and two years). Quality of life questions were compared between relevant pain at one year and two years.4.016 patients were included in the analysis. Mean age was 65.1 years, 90.3% of patients was male. Factors correlated with CPIP onset were age, gender, ASA, recurrent surgery, surgical technique, nerve handling and fixation type. Relevant pain at one month was a greater risk for CPIP than preoperative pain (12.3% vs 3.6%). In the majority of patients (83.2%) CPIP was ameliorated at two years. Hernia related complaints differed significantly between CPIP at one year and two years.Postoperative pain after one month was a greater risk factor for CPIP development than preoperative pain. CPIP at one year seems to have a different pain etiology than CPIP at two years. Patient and surgical factors influence the onset of CPIP at one year, however the natural course of these complaints shows great decline at two years, largely without reinterventions.
Use of Feeding Tubes in Nursing Home Residents With Severe Cognitive Impairment
Authors: Joan M. Teno
Journal: JAMA (2002)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Assessing Differences in Clinical Trials Comparing Surgical vs Nonsurgical Therapy
Authors: George Howard, Lloyd E. Chambless, Richard A. Kronmal
Journal: JAMA (1997)

The statement of hypotheses and choice of statistical tests in clinical trials that compare surgical with nonsurgical treatment are complicated by the likelihood of excess risk in the surgical group during the perioperative period but lower risk after that compared with the more uniform risk in the nonsurgical group. Commonly used statistical survival analyses implicitly assume a constant ratio of risks in the 2 groups during the follow-up period. However, the changing pattern of risk for one treatment but not the other implies that the assessment of the relative efficacy of the treatments varies with the length of the follow-up. As such, determining whether survival curves for the 2 groups are different may not translate easily into selecting the best treatment. Alternative statements of the hypothesis based on consideration of the time horizon of patients and on clinical judgment may be more consistent with the goals of the study. Regardless of the choice of a statistical test, the choice of treatment is a decision specific to the individual patient and should be influenced by the patient's life expectancy, attitude toward taking risks, quality of life, and cost considerations. When the survival curves cross, there is a trade-off between the risk of surgery and the increase in life expectancy among the survivors of surgery. Accordingly, assessment of differences in outcomes in clinical trials comparing surgical vs nonsurgical therapy should provide both a conclusion about whether 1 treatment can reasonably be considered best for most patients and should provide information to the individual patient and physician on the expected outcome to aid in the decision-making process.
HIV-1 Infection Among Intravenous Drug Users in Manhattan, New York City, From 1977 Through 1987
Authors: Don C. Des Jarlais
Journal: JAMA (1989)

Intravenous drug users are the second largest group to develop the acquired immunodeficiency syndrome, and they are the primary source for heterosexual and perinatal transmission in the United States and Europe. Understanding long-term trends in the spread of human immunodeficiency virus among intravenous drug users is critical to controlling the acquired immunodeficiency syndrome epidemic. Acquired immunodeficiency syndrome surveillance data and seroprevalence studies of drug treatment program entrants are used to trace seroprevalence trends among intravenous drug users in the borough of Manhattan. The virus entered this drug-using group during the mid-1970s and spread rapidly in 1979 through 1983. From 1984 through 1987, the seroprevalence rate stabilized between 55% and 60%—well below hepatitis B seroprevalence rates. This relatively constant rate is attributed to new infections, new seronegative persons beginning drug injection, seropositive persons leaving drug injection, and increasing conscious risk reduction. (<i>JAMA</i>1989;261:1008-1012)
<scp>FcεRI</scp>‐activated basophils express <scp>CCR4</scp>, <scp>CCR8</scp>, <scp>CCR9</scp>, <scp>CCX‐CKR</scp> and <scp>XCR1</scp>
Authors: Lars H. Blom, Ewa A. Bartko, Thea K. R. Møller, Lars K. Poulsen, Bettina M. Jensen
Journal: Allergy (2022)
<scp>IL1RAP</scp> expression and the enrichment of <scp>IL</scp>‐33 activation signatures in severe neutrophilic asthma
Authors: Yusef Eamon Badi, Barbora Salcman, Adam Taylor, Batika Rana, Nazanin Zounemat Kermani, John H. Riley, Sally Worsley, Sharon Mumby, Sven‐Eric Dahlen, David Cousins, Silvia Bulfone‐Paus, Karen Affleck, Kian Fan Chung, Stewart Bates, Ian M. Adcock
Journal: Allergy (2022)

Interleukin (IL)-33 is an upstream regulator of type 2 (T2) eosinophilic inflammation and has been proposed as a key driver of some asthma phenotypes.To derive gene signatures from in vitro studies of IL-33-stimulated cells and use these to determine IL-33-associated enrichment patterns in asthma.Signatures downstream of IL-33 stimulation were derived from our in vitro study of human mast cells and from public datasets of in vitro stimulated human basophils, type 2 innate lymphoid cells (ILC2), regulatory T cells (Treg) and endothelial cells. Gene Set Variation Analysis (GSVA) was used to probe U-BIOPRED and ADEPT sputum transcriptomics to determine enrichment scores (ES) for each signature according to asthma severity, sputum granulocyte status and previously defined molecular phenotypes.IL-33-activated gene signatures were cell-specific with little gene overlap. Individual signatures, however, were associated with similar signalling pathways (TNF, NF-κB, IL-17 and JAK/STAT signalling) and immune cell differentiation pathways (Th17, Th1 and Th2 differentiation). ES for IL-33-activated gene signatures were significantly enriched in asthmatic sputum, particularly in patients with neutrophilic and mixed granulocytic phenotypes. IL-33 mRNA expression was not elevated in asthma whereas the expression of mRNA for IL1RL1, the IL-33 receptor, was up-regulated in the sputum of severe eosinophilic asthma. The mRNA expression for IL1RAP, the IL1RL1 co-receptor, was greatest in severe neutrophilic and mixed granulocytic asthma.IL-33-activated gene signatures are elevated in neutrophilic and mixed granulocytic asthma corresponding with IL1RAP co-receptor expression. This suggests incorporating T2-low asthma in anti-IL-33 trials.
Is routine laboratory testing in healthy young patients taking isotretinoin necessary: a critically appraised topic
Authors: Andrew Affleck, David Jackson, Hywel C. Williams, Patricia Chavez, Joerg Albrecht
Journal: British Journal of Dermatology (2022)

Is monitoring of liver function, lipids and full blood count necessary in healthy people taking isotretinoin?Routine blood testing was recommended in the original licence for Roaccutane™ (isotretinoin) in 1983. In recent years, less frequent monitoring has been suggested by various authors.We performed four individual systematic searches of the MEDLINE database, via PubMed, from origin to 2 May 2021, supplemented by a hand search of all references in the identified papers.Inclusion criteria were any description of clinical symptoms, laboratory abnormalities and/or physical findings, and any paper that explicitly described the patients as asymptomatic, during treatment with oral isotretinoin.Two independent reviewers (J.A. and D.J.) assessed articles for eligibility of inclusion. Evaluation of the data was done also by two of the authors (A.A., D.J. and J.A.) for each section, with the aim to use the presented evidence including guidelines, databases, case series, case reports, cohort studies and randomized clinical trials to delineate the clinical presentation and frequency of adverse events that might be amenable to laboratory monitoring.We identified 407 papers in our searches and reviewed 125 papers in four sections. Overall, reported adverse events were very rare (< 1 in 10 000) and were either idiosyncratic or not preventable by monitoring, accompanied by symptoms, or seen in identifiable predisposed individuals who might benefit from monitoring because of pre-existing conditions.We could not find evidence to support the benefit of monitoring to detect adverse events. We suggest that in healthy young people laboratory monitoring for oral isotretinoin is unnecessary and risks detecting nonserious biochemical abnormalities. However, we recognize that new information about adverse events may change that recommendation.
Incidence of Adverse Drug Events and Potential Adverse Drug Events
Authors: David W. Bates
Journal: JAMA (1995)

<h3>Objectives.</h3> —To assess incidence and preventability of adverse drug events (ADEs) and potential ADEs. To analyze preventable events to develop prevention strategies. <h3>Design.</h3> —Prospective cohort study. <h3>Participants.</h3> —All 4031 adult admissions to a stratified random sample of 11 medical and surgical units in two tertiary care hospitals over a 6-month period. Units included two medical and three surgical intensive care units and four medical and two surgical general care units. <h3>Main Outcome Measures.</h3> —Adverse drug events and potential ADEs. <h3>Methods.</h3> —Incidents were detected by stimulated self-report by nurses and pharmacists and by daily review of all charts by nurse investigators. Incidents were subsequently classified by two independent reviewers as to whether they represented ADEs or potential ADEs and as to severity and preventability. <h3>Results.</h3> —Over 6 months, 247 ADEs and 194 potential ADEs were identified. Extrapolated event rates were 6.5 ADEs and 5.5 potential ADEs per 100 nonobstetrical admissions, for mean numbers per hospital per year of approximately 1900 ADEs and 1600 potential ADEs. Of all ADEs, 1% were fatal (none preventable), 12% life-threatening, 30% serious, and 57% significant. Twenty-eight percent were judged preventable. Of the life-threatening and serious ADEs, 42% were preventable, compared with 18% of significant ADEs. Errors resulting in preventable ADEs occurred most often at the stages of ordering (56%) and administration (34%); transcription (6%) and dispensing errors (4%) were less common. Errors were much more likely to be intercepted if the error occurred earlier in the process: 48% at the ordering stage vs 0% at the administration stage. <h3>Conclusion.</h3> —Adverse drug events were common and often preventable; serious ADEs were more likely to be preventable. Most resulted from errors at the ordering stage, but many also occurred at the administration stage. Prevention strategies should target both stages of the drug delivery process. (<i>JAMA</i>. 1995;274:29-34)
Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy
Authors: Zaigang Zhou, Jiashe Chen, Yu Liu, Chunjuan Zheng, Wenjuan Luo, Lele Chen, Shen Zhou, Zhiming Li, Jianliang Shen
Journal: Acta Pharmaceutica Sinica B (2022)

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles
Honokiol alleviated neurodegeneration by reducing oxidative stress and improving mitochondrial function in mutant SOD1 cellular and mouse models of amyotrophic lateral sclerosis
Authors: Yujun Zhou, Jingshu Tang, Jiaqi Lan, Yong Zhang, Hongyue Wang, Qiuyu Chen, Yuying Kang, Yang Sun, Xinhong Feng, Lei Wu, Hongtao Jin, Shizhong Chen, Ying Peng
Journal: Acta Pharmaceutica Sinica B (2022)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.
Azithromycin promotes relapse by disrupting immune and metabolic networks after allogeneic stem cell transplantation
Authors: Nicolas Vallet, Sophie Le Grand, Louise Bondeelle, Bénédicte Hoareau, Aurélien Corneau, Delphine Bouteiller, Simon Tournier, Lucille Derivry, Armelle Bohineust, Marie Tourret, Delphine Gibert, Ethan Mayeur, Raphael Itzykson, Kim Pacchiardi, Brian Ingram, Stéphane Cassonnet, Patricia Lepage, Régis Peffault de Latour, Gérard Socié, Anne Bergeron, David Michonneau
Journal: Blood (2022)
Noncanonical EZH2 drives retinoic acid resistance of variant acute promyelocytic leukemias
Authors: Mathilde Poplineau, Nadine Platet, Adrien Mazuel, Léonard Hérault, Lia N’Guyen, Shuhei Koide, Yaeko Nakajima-Takagi, Wakako Kuribayashi, Nadine Carbuccia, Loreen Haboub, Julien Vernerey, Motohiko Oshima, Daniel Birnbaum, Atsushi Iwama, Estelle Duprez
Journal: Blood (2022)

Cancer cell heterogeneity is a major driver of therapy resistance. To characterize resistant cells and their vulnerabilities, we studied the PLZF-RARA variant of acute promyelocytic leukemia, resistant to retinoic acid (RA), using single-cell multiomics. We uncovered transcriptional and chromatin heterogeneity in leukemia cells. We identified a subset of cells resistant to RA with proliferation, DNA replication, and repair signatures that depend on a fine-tuned E2F transcriptional network targeting the epigenetic regulator enhancer of zeste homolog 2 (EZH2). Epigenomic and functional analyses validated the driver role of EZH2 in RA resistance. Targeting pan-EZH2 activities (canonical/noncanonical) was necessary to eliminate leukemia relapse-initiating cells, which underlies a dependency of resistant cells on an EZH2 noncanonical activity and the necessity to degrade EZH2 to overcome resistance. Our study provides critical insights into the mechanisms of RA resistance that allow us to eliminate treatment-resistant leukemia cells by targeting EZH2, thus highlighting a potential targeted therapy approach. Beyond RA resistance and acute promyelocytic leukemia context, our study also demonstrates the power of single-cell multiomics to identify, characterize, and clear therapy-resistant cells.
Genetic predisposition to porto‐sinusoidal vascular disorder: A functional genomic‐based, multigenerational family study
Authors: Jingxuan Shan, André Megarbane, Aziz Chouchane, Deepak Karthik, Ramzi Temanni, Atilio Reyes Romero, Huiying Hua, Chun Pan, Xixi Chen, Murugan Subramanian, Chadi Saad, Hamdi Mbarek, Cybel Mehawej, Eliane Chouery, Sirin W. Abuaqel, Alexander Dömling, Sami Remadi, Cesar Yaghi, Pu Li, Lotfi Chouchane
Journal: Hepatology (2022)

Porto-sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease.We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 ( FCHSD1 ), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C-to-T substitution at position 547, corresponding to FCHSD1R183W , may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR-associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein.Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.